Dry powder inhalers have been developed as an alternative to Metered dose inhaler (MDI) devices and offer a number of advantages over the latter; principally the reduced need for patient co-ordination since the drug is expelled from the device as a result of the patient’s own aspiratory effort. However, dry powder formulation need to be stable for a period of time and in different climatic conditions such as 25 ºC and 75 % Relative humidity (RH). Therefore the aim of this study was to produce stable Ipratropium Bromide-Multidose dry powder inhaler (IPR-MDPI) using different types of lactose that meets European Pharmacopoeia/United States Pharmcopoeia (EP/USP) requirements after 3 months storage at 25 ºC, 75 % RH. Mixture of α-lactose and micronized ß-lactose were used to prepare two Ipratropium Bromide formulations and they were IPR -01 and IPR -01R. Α-lactose (Foremost Aeroflo 65) was used to prepare two formulations and they were IPR-02 and IPR-02R. All four blends were then tested according to EP/USP guidelines for mass delivery, dose content uniformity, total dose (TD), fine particle dose (FPD) and fine particle fraction (FPF) at time point zero (t=0). These formulations were put on the stability trial at 25 ºC, 75 % RH (unwrapped), 30 ºC, 60 % RH (unwrapped) and 40 ºC, 75 % RH (wrapped) respectively. Batch-to-batch reproducibility between the repeat blends was good, with similar performance data. Both formulation approaches showed similar trends in pharmaceutical performance over the lifetime of the stability trial. Drug per actuations (DPA) were within EP/USP guidelines over the 2/3 months of the stability trials, despite a small rise in DPA over the lifetime of the trial and the lifetime of the device. The average DPAs over all stability conditions and time points were: 21.1 1.7 g (IPR-01 and IPR-01R) and 20.9 1.5 g (IPR-02 and IPR-02R). However, the increases seen in DPA meant that the DPAs did not pass the tougher specifications of the Food and Drug Administration Authority (FDA) (Dose Content Uniformity, DCU limits). FPDs remained stable and high for all formulations (10.5 1.0 g). FPF fell initially between t = 0 and t = 1 month, but the FPF value stabilized reaching an equilibrium value (45–49 %) between t = 1 and t = 2/3 months. Performance appeared independent of stability conditions (including wrapped and unwrapped), although dose consistency was slightly more variable at 25 ºC, 75 %RH for both formulations. The /-lactose IPR-MDPIs showed slightly less variation in DPA and FPD over the lifetime of the stability trials, but the pure -lactose IPR-MDPIs produce higher FPDs. The present research showed that the two lead IPR-MDPI approaches (-Lactose (Borculo) + 2.5 wt. % micronised -lactose + 1 wt. % IPR and -Lactose (Foremost Aeroflo 65) + 1 wt. % IPR) show encouraging stability trends at all three stability conditions on the basis of their pharmaceutical performance.
Loading....